Undetected primary aldosteronism: study findings a ‘game changer’

By Nicole MacKee
‘Game-changing’ research showing a high and undetected prevalence of primary aldostero­nism will prompt a ‘radical reappraisal’ of diagnosis and management, a leading Australian expert says.

The cross­-sectional US study, published in the Annals of Internal Medicine, evaluated primary aldosteronism in 1015 eligible participants (289 untreated, normotensive people; 115 people with stage 1 hypertension; 203 with stage 2 hypertension; and 408 with resistant hypertension).

Current guidelines recommend screening for primary aldosteronism by measuring aldosterone–renin ratio (ARR) in patients with severe hypertension or with hypertension coupled with hypokalaemia, sleep apnoea or an adrenal mass.

However, for this study, the researchers evaluated participants for the presence of nonsuppressible renin-independent aldoste­rone production in 24­-hour urine collections, regardless of ARR. They found a continuum of urinary aldosterone excretion in parallel with the severity of hypertension and a ‘much higher’ prevalence of primary aldosteronism than normally seen in each blood pressure category (ranging from 11.3% in normotensive patients to 22% in patients with resistant hypertension).

‘These findings redefine the primary aldosteronism syndrome and implicate it in the pathogenesis of “essential” hypertension,’ the researchers concluded.

Professor John Funder, from the Hudson Institute of Medical Research, Melbourne, and author of an editorial accompanying the research, wrote that using a 24-hour urine sample detected a prevalence of primary aldosteronism that was three to five times that detected using a conventional spot-testing of plasma aldosterone concentration.

He wrote that a single morning spot measurement of aldosterone could not take into account ultradian variation in aldosterone secretion.

‘The other problem is that fewer than 1% of people with primary aldosteronism are ever screened, let alone diagnosed,’ he told Medicine Today.

Professor Funder said these findings, with those of smaller studies going back 40 years, would put the prevalence of primary aldosteronism in hypertension at 30 to 50%.

‘That’s half a billion people around the world,’ he said. ‘And they are in double jeopardy because we know that high blood pressure increases morbidity and mortality risks and having unrecognised and untargeted primary aldosteronism further increases these mortality rates threefold.’

Professor Funder said GPs would need to lead the change in screening. He recommended that before prescribing antihyper­tensives for a newly diagnosed patient, the GP sends a blood sample for plasma renin measurement.

‘If renin is suppressed – as in the Annals study – the patient collects their urine over 24 hours for measurement of aldosterone excretion. For patients already taking antihypertensives, addition of low-dose targeted aldosterone blocker may sort out who has primary aldosteronism, and who does not, on the basis of their blood pressure response,’ Professor Funder said.
Ann Intern Med 2020; [e-pub]; https://doi.org/10.7326/M20-0065.
Ann Intern Med 2020; [e-pub]; https://doi.org/10.7326/M20-1758.